{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Musille PM"],"funding":["American Heart Association","National Institute of Environmental Health Sciences","Department of Energy, Labor and Economic Growth","NIDDK NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases","NIEHS NIH HHS","National Institute of General Medical Sciences","NIGMS NIH HHS","National Science Foundation"],"pagination":["1411-26"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4714224"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["291(3)"],"pubmed_abstract":["Phospholipids (PLs) are unusual signaling hormones sensed by the nuclear receptor liver receptor homolog-1 (LRH-1), which has evolved a novel allosteric pathway to support appropriate interaction with co-regulators depending on ligand status. LRH-1 plays an important role in controlling lipid and cholesterol homeostasis and is a potential target for the treatment of metabolic and neoplastic diseases. Although the prospect of modulating LRH-1 via small molecules is exciting, the molecular mechanism linking PL structure to transcriptional co-regulator preference is unknown. Previous studies showed that binding to an activating PL ligand, such as dilauroylphosphatidylcholine, favors LRH-1's interaction with transcriptional co-activators to up-regulate gene expression. Both crystallographic an"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Unexpected Allosteric Network Contributes to LRH-1 Co-regulator Selectivity."],"pmcid":["PMC4714224"],"funding_grant_id":["R01GM110387","T32ES012870","T32 ES012870","12PRE12060583","R01 DK095750","R01DK095750","R01 GM110387","DE-AC02–05CH11231","MCB-1149521"],"pubmed_authors":["Kossmann BR","Ortlund EA","Kohn JA","Ivanov I","Musille PM"],"additional_accession":[]},"is_claimable":false,"name":"Unexpected Allosteric Network Contributes to LRH-1 Co-regulator Selectivity.","description":"Phospholipids (PLs) are unusual signaling hormones sensed by the nuclear receptor liver receptor homolog-1 (LRH-1), which has evolved a novel allosteric pathway to support appropriate interaction with co-regulators depending on ligand status. LRH-1 plays an important role in controlling lipid and cholesterol homeostasis and is a potential target for the treatment of metabolic and neoplastic diseases. Although the prospect of modulating LRH-1 via small molecules is exciting, the molecular mechanism linking PL structure to transcriptional co-regulator preference is unknown. Previous studies showed that binding to an activating PL ligand, such as dilauroylphosphatidylcholine, favors LRH-1's interaction with transcriptional co-activators to up-regulate gene expression. Both crystallographic an","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jan","modification":"2025-04-19T08:34:09.485Z","creation":"2019-03-27T02:06:56Z"},"accession":"S-EPMC4714224","cross_references":{"pubmed":["26553876"],"doi":["10.1074/jbc.M115.662874","10.1074/jbc.m115.662874"]}}